tbuckley/cabot-search huggingface dataset:
SURG-05. Survival and functional outcomes in pediatric thalamic and thalamopeduncular low grade gliomas
Authors: Vladimir Benes, Michal Zapotocky, Petr Liby, Jakub Taborsky, Jana Blazkova Jr., Jana Blazkova Sr., David Sumerauer, Adela Misove, Ivana Pernikova, Martin Kyncl, Lenka Krskova, Miroslav Koblizek, Josef Zamecnik, Ondrej Bradac, Michal Tichy
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Childhood thalamopeduncular gliomas arise at the interface of thalamus and cerebral peduncle. The optimal treatment is total resection but not at the cost of neurological function. We present long-term clinical and oncological outcomes of maximal safe resection. METHODS: Retrospective review of prospectively collected data: demography, symptomatology, imaging, extent of resection, surgical complications, histology, functional and oncological outcome. RESULTS: During 16-year period (2005-20) 21 patients were treated at our institution. These were 13 girls and 8 boys (mean age 7.6 years). Presentation included progressive hemiparesis in 9 patients, raised intracranial pressure in 9 patients and cerebellar symptomatology in 3 patients. The tumor was confined to the thalamus in 6 cases. Extent of resection was judged on postoperative imaging as total (6), near-total (6) and less extensive (9). Surgical complications included progression of baseline neurological status in 6 patients, 5 of these gradually improved to preoperative status. All tumors were classified as low-grade gliomas. Disease progression was observed in 9 patients (median progression free survival 7.3 years). At last follow-up (median 6.1 years) all patients were alive; median Lansky score of 90. Seven patients were without evidence of disease, 6 had stable disease, 7 stable following progression and 1 had progressive disease managed expectantly. CONCLUSION: Pediatric patients with low grade thalamopeduncular gliomas have excellent long-term functional and oncological outcomes even when gross total resection is not achievable. Surgery should aim at total resection; however neurological function should not be endangered due to excellent chance for long-term survival.
Real-world analysis of safety and efficacy of CAR T-cell therapy in patients with lymphoma with decreased renal function.
Authors: Omar Mamlouk, Paolo Strati, Lei Feng, Ryan Sun, Raphael Eric Steiner, Ranjit Nair, Christopher Flowers, Jeremy L Ramdial, Neeraj Saini, Samer Ali Srour, Richard E. Champlin, Partow Kebriaei, Loretta J. Nastoupil, Maria Alma Rodriguez, Elizabeth J. Shpall, Yago Nieto, Jason Westin, Sattva Swarup Neelapu, Sreedhar Mandayam, Sairah Ahmed
Journal: Journal of Clinical Oncology (2022)

7536 Background: Chimeric antigen receptor T-cell therapy (CART) is approved for treatment of relapsed and refractory large B cell lymphoma (r/r LBCL), however eligibility for patients (pts) treated on clinical trials included normal kidney function (NKF). There is a gap in knowledge regarding the safety and efficacy of CART in pts with reduced kidney function (RKF), despite the prevalence of chronic kidney disease in lymphoma pts. Methods: This is a single-center retrospective analysis of adult pts with r/r LBCL who received CART between 2017-2021. RKF was defined as estimated glomerular filtration rate (GFR) of &lt; 60 ml/min and NKF defined as GFR ≥ 60 ml/min, at time of lymphodepletion chemotherapy (LDC). Increased length of ICU stay define as &gt; 3 days. Kaplan-Meier method used to estimate the time-to-event endpoints including progression free survival (PFS), and overall survival (OS). Results: We identified 210 pts who received CART, of those 169 (80.5%) had NKF and 41(19.5%) had RKF (15-59 ml/min, 27% &lt; 45). Median age of pts was 60 and 63% of RKF pts were older than 60 vs 45% in NKF group (p = 0.03). Median Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score of pts with RKF was higher than NKF (3 vs. 1, P = 0.004). Pts with RKF had significantly longer ICU length of stay (29.3% vs. 13.6%; p = 0.01). There was no difference in grade 3 hematological toxicity (82.9% vs. 84.5%, p = 0.80) or infection within 30 days of CART (51.2% vs. 37.9%, p = 0.11) between RKF and NKF pts, respectively. CART specific toxicity including grade and frequency of cytokine release syndrome and neurotoxicity was also not related to renal function. After a median follow-up of 22.9 months (95% CI: 21.1-25.6 months), there was no significant difference in PFS and OS when comparing pts with RKF vs. NKF; PFS at 1 year of 31% (19-50%) vs. 33% (26-41%), p = 0.97, and OS at 1 year was 47% (34-67%) vs. 44% (37-57%), p = 0.45, and respectively. However, pts with RKF had a significant increase in non-relapse mortality (NRM) at 3 months (19.5% vs. 8.3%, p = 0.03), and at 6 months (22% vs. 9.5%, p = 0.02), respectively. Conclusions: In this retrospective single center study we observed reassuring durable remission rates in pts with r/r LBCL and RKF who received CART, without significantly different PFS or OS. Interestingly our analysis found that increased ICU length of stay and higher rates of NRM early after CART were associated with RKF. While our data shows RKF does not preclude pts from receiving CART for r/r LBCL, it does suggest that patients with RKF may need closer monitoring and multidisciplinary management.
DIPG-60. Avapritinib for targeting PDGFRA in H3K27M – mutated diffuse midline glioma
Authors: Lisa Mayr, Sibylle Madlener, Liesa Weiler-Wichtl, Verena Rosenmayr, Julia Furtner-Srajer, Armin Guntner, Natalia Stepien, Alicia-Christina Baumgartner, Christian Dorfer, Christine Haberler, Leonhard Müllauer, Hana Palova, Petra Pokorna, Jaroslav Sterba, Karin Dieckmann, Amedeo Azizi, Andreas Peyrl, Sean Kim, Antony Hsieh, Sasa Dimitrijevic, Johannes Gojo
Journal: Neuro-Oncology (2022)

Abstract H3K27M-mutated diffuse midline glioma (H3K27M DMG) are an almost universally fatal disease with a median survival of less than 6 months post progression and no effective therapy. PDGFRA-signaling has shown to promote and sustain a subset of oligodendrocyte precursor-like tumor cells that are responsible for tumor propagating potential and high proliferation rates. However, first attempts to target PDGFRA in adult glioblastoma with dasatinib/imatinib or pediatric refractory brain tumors with sunitinib were not successful. We report on the first experience in two patients receiving avapritinib, a highly potent, selective, brain penetrant PDGFRA/KIT inhibitor under a compassionate use program. Our first patient with spinal H3K27M DMG developed supratentorial metastases ten months after initial diagnosis. Molecular profiling revealed de novo PDGFRA and KIT amplifications and treatment with dasatinib was initiated. Due to disease progression and novel metastases, therapy was switched to avapritinib showing near complete resolution of the previously unirradiated frontal lesion with additional disease stabilization of other metastatic sites. Following re-resection and irradiation of progressing cerebellar lesions, the patient remains clinically stable on avapritinib therapy over 12 months. The second patient with diffuse intrinsic pontine glioma showed disease progression nine months after diagnosis and was treated with focal re-irradiation (30Gy). As the tumor harbored a PDGFRA R841del alteration, avapritinib was initiated seven weeks after radiation upon further tumor progression resulting in partial response. Pharmacokinetic sampling of cerebrospinal fluid (CSF) detected an increasing CSF/plasma ratio over time and up to 4 µM avapritinib in tumor tissue. Avapritinib CSF levels in both patients were distinctly higher than dasatinib levels. Avapritinib was generally well tolerated besides lower limb edema, elevated LDH and liver enzymes. Hence, effective CNS penetration of avapritinib at pharmacologically relevant brain tumor concentrations resulted in clinical response in two patients with rapidly progressive H3K27M DMG.
Resolution of Misleading COVID-19 Vaccination–Related Nodal and Splenic FDG Uptake in the Follow-up Study
Authors: Sudhir Bhimaniya, Amin Jahromi
Journal: Clinical Nuclear Medicine (2022)

Abstract Newly diagnosed low-grade bilateral breast lymphoma in 63-year-old woman demonstrated intense FDG uptake in the left axillary lymph nodes and the spleen, concerning for lymphomatous involvement. Subsequent ultrasound-guided biopsy did not demonstrate any pathologic left axillary lymph nodes. Further investigation revealed COVID-19 vaccination in the left arm, 5 days prior to the 18 F-FDG PET/CT study. Six-month follow-up 18 F-FDG PET/CT showed resolution of the intense FDG uptake in the left axillary lymph nodes and spleen without any treatment, suggesting a self-remitting acute local and systemic immune response to COVID-19 vaccination.
Electronic capture of cancer-related distress in a community oncology program.
Authors: Amit Sanyal, Heather Bowen, Clemens Walter Janssen, Alissa Ashley Weber
Journal: Journal of Clinical Oncology (2022)

1577 Background: Cancer related distress can be seen in as many as one in two patients. Many organizations such as the Commission on Cancer require distress screening. National Comprehensive Cancer Network (NCCN) distress thermometer is a common tool used for screening. We studied feasibility of embedding the NCCN thermometer into oncology electronic health record (EHR) for routine patient care. We concurrently studied feasibility of using a mobile health tool for serial evaluation of cancer related distress. Methods: A flowsheet containing NCCN distress thermometer questions was created in Epic EHR (Epic Systems, Verona, WI). Oncology nurses used the flowsheet for routine patient assessment. Patients with distress level ≥ 4 answered additional questions. Ancillary care providers such as palliative care nurses or social workers addressed the identified needs by providing appropriate ‘services’. A field to capture these interventions was created. We also adapted our previously reported web based mobile tool [1] for monitoring cancer distress. Patients rated their distress on a 1-10 scale and highlighted the distress domain (physical, emotional, practical, family). Distress level ≥ 4 generated a color-coded flag for provider review and intervention. Data from both electronic tools was periodically analyzed to inform patient care and quality improvement. Results: Between January and December 2021, Epic EHR based distress flowsheet collected 28,594 distinct responses in 911 patients. 57.4%, 14.9%, 14.1%, 9.4% and 2.3% of the responses were in the physical, emotional, practical, familial and spiritual domains respectively. ‘Other’ responses were 1.4%. Cumulative frequency of non-physical problems was 42.5%. 1819 ‘services’ were provided with 357 emotional, 351 work, 351 housing, 350 transportation and 350 financial need-based interventions. Of 1231 patients who used the distress scale and provided additional comments, 315 (25.5%) had distress levels ≥ 4. The mobile tool captured 849 unique patient responses to the distress question between April 2020 and February 2022. Distress level ≥ 4 was flagged by 281 unique patients (33.09%). Average distress level was 2.7. Emotional domain problems generated the greatest distress level followed by family, physical and practical problems in decreasing order. Conclusions: We demonstrate feasibility of electronic capture of cancer related distress to facilitate holistic patient care in a community-based oncology program. EHR based and mobile tool distress evaluations generated concordant results. Distress caused by emotional, practical and familial domain problems was nearly as frequent and often more severe than distress caused by physical problems, underscoring the need for comprehensive cancer care. References:Sanyal, A. Mobile health tool for monitoring cancer treatment complications. 2020 ASCO Quality Care Symposium: American Society of Clinical Oncology.
Prognostic impact of systemic anti-cancer therapy on patients with advanced cancer at end of life: Analysis of a multicenter prospective cohort study using propensity score methods.
Authors: Shuji Hiramoto, Kiyofumi Oya, Rie Tokutani, Toshihiko Kirishima, Isseki Maeda, Hori Tetsuo, Koji Amano, Toshihiro Yamauchi, Yusuke Hiratsuka
Journal: Journal of Clinical Oncology (2022)

12029 Background: Prognosis is said to worsen when systemic anti-cancer therapy (SACT) is administered until a patient’s end of life (EOL) and professional palliative care is delayed. However, the prognostic impact of SACT at EOL is unclear. Methods: In this pre-planned secondary analysis of a multicenter, prospective East Asian cross-cultural collaborative cohort study, consecutive patients with advanced cancer admitted to palliative care units between January and December 2017 were divided into four groups: patients who had and had not received SACT (SACT vs. non-SACT) and patients whose last administration of SACT was before or within 1 month of study enrolment (non-1M SACT vs. 1M SACT). The primary endpoint was difference in survival time from a palliative performance scale (PPS) of &lt; 20 to death between the SACT and non-SACT groups, and the 1M SACT and non-1M SACT groups. The analysis was adjusted for age; sex; primary cancer site; metastatic site; comorbidity (Charlson comorbidity index); and history of radiotherapy, smoking, and psychiatric disorders. Weighting for inverse probability of treatment was applied. A secondary endpoint was to identify EOL symptom and care factors prognostic for survival time using a Cox proportional hazards model. Results: The 1396 study patients (712 men, 684 women; median age: 73 years) came from 21 institutions throughout Japan. Primary tumor sites were upper gastrointestinal (471 patients), lower gastrointestinal (193 patients), lung (241 patients), breast (93 patients), urologic (101 patients), gynecologic (82 patients), head and neck (56 patients), central nervous system (25 patients), and hematologic (39 patients). Metastatic sites were liver (554 patients), lung (522 patients), bone (373 patients), and brain (199 patients). The SACT, non-SACT, 1M SACT, and non-1M SACT groups consisted of 853, 539, 126, and 1270 patients, respectively. Survival time was significantly shorter in the SACT group (6.83 days, p = 0.03) than in the non-SACT group (9.01 days). No significant difference between the 1M SACT group (7.57 days) and the non-1M SACT group (7.36 days) was evident. Prognostic factors were use of opioids (HR 1.289), antipsychotics (HR 0.787), and anxiolytics (HR 0.867); infusion of more than 1 L daily (HR 0.727); and apnea (HR 0.874), dyspnea (HR 1.874), nausea (HR 0.612), fatigue (HR 1.284), and ascites (HR 1.236). Conclusions: Prognosis was shorter for patients with a history of SACT than for those without a history of SACT at EOL. However, SACT at EOL was not a prognostic factor. This information is useful in advance care planning for selecting and explaining treatment at EOL to patients and their families.
A phase 3, randomized, open-label study of the anti-Globo H vaccine adagloxad simolenin/obi-821 in the adjuvant treatment of high-risk, early-stage, Globo H-positive triple-negative breast cancer.
Authors: Hope S. Rugo, Javier Cortes, Binghe Xu, Chiun-Sheng Huang, Sung-Bae Kim, Michelle E. Melisko, Rita Nanda, Priyanka Sharma, Richard Schwab, Pei Hsu
Journal: Journal of Clinical Oncology (2022)

TPS611 Background: Adagloxad simolenin (A-S) is an anti-Globo H immunogen comprised of the carbohydrate tumor antigen Globo H, covalently linked to keyhole limpet hemocyanin, a carrier protein that deploys T cells to enhance the humoral response. Administration of A-S in combination with the immune adjuvant OBI-821 serves as an anti-tumor associated carbohydrate antigen vaccine intended to generate anti-Globo H humoral responses in patients with Globo H-expressing tumors. Methods: Study OBI-822-011, a phase 3 study, was initiated in 2018. Following feedback from investigators and advisors the study design was changed from a double-blind, placebo-controlled study to an open-label, standard of care (SOC) study. The revised protocol includes patients who have recovered from surgery and completed all planned neoadjuvant and/or adjuvant multiagent chemotherapy and/or radiation therapy. SOC in the A-S/OBI-821 arm is concomitant therapy of capecitabine or immune checkpoint inhibitor. In the SOC arm patients will receive SOC therapy consisting of observation alone, or adjuvant capecitabine alone, or immune checkpoint inhibitor alone. The key protocol changes included a change from open-label to standard of care, providing unblinding and reconsent guidelines for patients enrolled into the study prior to the protocol amendment, allowing concurrent adjuvant single agent chemotherapy, revising the stratification algorithm from a non-hierarchical to a hierarchical structure and aligning the stratification factors with prognostic factors more representative of the study population, revising the eligibility criteria, number and frequency of assessments to reduce patient burden, revising the interim analysis timepoints for futility, and removed an interim analysis for superiority. Study Objectives: Primary Objective: To determine the effect of A-S/OBI-821 treatment on improving IDFS in the study population. Secondary Objectives: To determine the impact of A-S/OBI-821 treatment on Overall survival (OS), Quality of life (QoL), Breast cancer-free interval (BCFI), Distant disease-free survival (DDFS) in the study population; To determine the safety and tolerability of A-S/OBI-821 in the study population. Key Exploratory Objectives: Beyond the safety, efficacy, and QoL endpoints of this trial, exploratory endpoints will evaluate the relationship between aberrant Globo H expression and baseline characteristics, including tumor pathology and immune factors. Conclusion: An estimated 668 subjects will be enrolled, treated for up to 2 years, and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last subject randomized. Survival follow-up is for 5 years from randomization of last subject. Clinical trial information: NCT03562637.
Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation
Authors: Ananda S. Mirchandani, Stephen J. Jenkins, Calum C. Bain, Manuel A. Sanchez-Garcia, Hannah Lawson, Patricia Coelho, Fiona Murphy, David M. Griffith, Ailiang Zhang, Tyler Morrison, Tony Ly, Simone Arienti, Pranvera Sadiku, Emily R. Watts, Rebecca. S. Dickinson, Leila Reyes, George Cooper, Sarah Clark, David Lewis, Van Kelly, Christos Spanos, Kathryn M. Musgrave, Liam Delaney, Isla Harper, Jonathan Scott, Nicholas J. Parkinson, Anthony J. Rostron, J. Kenneth Baillie, Sara Clohisey, Clare Pridans, Lara Campana, Philip Starkey Lewis, A. John Simpson, David H. Dockrell, Jürgen Schwarze, Nikhil Hirani, Peter J. Ratcliffe, Christopher W. Pugh, Kamil Kranc, Stuart J. Forbes, Moira K. B. Whyte, Sarah R. Walmsley
Journal: Nature Immunology (2022)

Abstract Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.
Applicability of a web app for breast cancer risk calculation and personalized recommendations for screening in Mexico.
Authors: Jose Felipe Muñoz Lozano, Omar A. Zayas, Carlos Eduardo Salazar-Mejía, Victor Oyervides, Oscar Vidal-Gutiérrez, Rafael Pineiro-Retif, Brenda Garza, Ricardo Andres Gomez, Larisa Renteria, Diana Cristina Pérez-Ibave
Journal: Journal of Clinical Oncology (2022)

1567 Background: A minority of women with breast cancer in Mexico are being diagnosed through a screening program, which translates into late diagnosis and a worse prognosis. It is imperative to develop easy access and low-cost interventions to increase the screening rate. Methods: We developed a web app tailored to guide patients to seek medical consultation if they were at high risk for breast cancer or standard screening recommendations based on the predicted risk for age (https://cuccuanl.com/calcula-tu-riesgo-de-cancer-de-mama/). The web app consisted of an 8-question survey designed using object-based programming with HTML5, the additional logic was programmed on JavaScript. The program logic automatically guided patients to medical consultation if they were at high risk for breast cancer, or standard screening recommendations based on their predicted risk for age. On each confirmation page, the contact information of the hospital appeared, also, consultation at the clinic could be scheduled within the web app. The web app was distributed via social media on International Breast Cancer Awareness Day. Results: A total of 1,012 persons answered the survey after a follow-up period of two weeks. The median age of respondents was 34 years. Among participants, 10.8% were considered at very high risk for breast cancer due to symptoms, 22% were classified as high risk based on family history or more than 5 years of contraceptive use, and 19% were considered as average-risk population for whom age-based screening tests were recommended. The remaining 48% of participants were considered at low risk for breast cancer development and were directed to educational information about breast cancer awareness. Among all persons that answered our survey, 21 requested a specialized medical appointment within the web app. Conclusions: This pilot study showed a high response of Mexican population seeking breast cancer risk evaluation, 11% of women that responded to our survey had symptoms highly suggestive of breast cancer. The use of web apps can result in mass diffusion which will help reach people with less medical access, a common scenario in many developing countries. Further analysis should be made to measure the real impact on breast cancer diagnosis and oncological outcomes. This study shows how effective social media is as a means of diffusion on health topics. [Table: see text]